Atrial fibrillation (AF) is the most prevalent clinical arrhythmia in clinical practice and a major contributor to morbidity and mortality. A recent study estimated that the number of Americans afflicted by AF will increase from the current range of 2.2 to 5.6 million to more than 12 million by 2050. This increase will be driven significantly by demographics, since AF affects nearly 4% of the US population over 60 years of age. The enormity of the clinical problem is magnified by well-described sequelae: thromboembolic stroke, congestive heart failure (CHF), increased mortality and cognitive dysfunction. According to a recent report by the AF StatTM working group, AF costs Medicare more than $ 15.7 billion annually due to costly complications. This grant specifically proposes a new enhanced atrial defibrillator system, which is intended eventually for human use as an implantable device. The system is designed for delivery of sequential low-voltage multiple pulse shocks. The efficacy and cardiac safety using the enhanced atrial system will be tested in a chronic pacing animal model. An effective atrial defibrillator that could successfully employ low energy, painless shocks will be a valuable addition to existing implantable devices such as dual chamber pacemakers and defibrillators. We hypothesize that AF internal conversion to normal sinus rhythm is possible using voltage levels that will not be perceived by the patient. To date, clinical applications have not reached this potential. The hypothesis is the following: Low-voltage shock, applied as monophasic or biphasic waveforms in multiple pulses, can induce virtual electrode polarization (VEP) at the anatomical heterogeneities. VEP can be used to destabilize and halt reentrant circuits. The strategy is to demonstrate that phase-dependent low voltage multiple pulses with energy below single pulse defibrillation thresholds and above current magnitudes for anti-tachycardia pacing, applied on a far field basis to unpin reentry and errant circuits pinned to heterogeneities, can achieve significant reductions of voltage levels required for atrial defibrillation. In our experiments, the low-energy shocks will incorporate phased unpinning far-field therapy comprising multiple pulses of between 0.02 and 0.1 J, delivered through at least three electrodes, so as to generate a virtual electrode polarization or rotating field. We have now successfully completed an acute atrial defibrillation animal study using a canine vagally- mediated AF model to test the feasibility of this theory. The data from this work has proven the concept that low energy shocks incorporating phased, biphasic waveforms can safely achieve internal cardioversion for AF on an effectively low-voltage level. The averaged atrial DFT level is at 40 V (~0.1 J) among the three vectors tested (SVC to CS, CS to LAA, and RAA to LAA). With waveform optimization and electrodes orientation, low voltage shocks can be further decreased below 0.1 J to ensure that the new modality remains pain-free. The results encourage us to develop and examine a novel enhanced atrial defibrillation system, which can deliver low voltage multiple pulse waveform as well as standard single biphasic waveform shock therapy. Specifically we will design and build circuitry and algorithms for a research external defibrillator that can deliver a traditional waveform, as well as novel multiple-pulse waveforms. This design will utilize waveform shaping circuitry that has been utilized previously in industrial applications but has not been adapted for use in medical devices. The functionality of the prototype external system, pacing leads, and algorithms will be tested in a chronic pacing canine AF model and then efficacy and safety of multiple-pulse waveform will be compared versus the traditional biphasic truncated exponential waveform. It is anticipated that the proposed new study will provide fundamentally important insights into the hypothesis that multiple phased low-energy shocks can safely achieve internal cardioversion for AF. We expect the study is a big step forward from the "VEP and unpinning" theory to an atrial defibrillator clinical development. If the enhanced system is effective and safe for defibrillation, it should advance commercial product development for the low voltage multiple pulse AF devices and this will open up a new avenue for AF treatment.